6-amino-5-(benzylamino)-3-methylpyrimidine-2,4(1H,3H)-dione | 2034-31-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 6-amino-5-(benzylamino)-3-methylpyrimidine-2,4(1H,3H)-dione
• 英文别名: 6-amino-5-benzylamino-3-methyl-1H-pyrimidine-2,4-dione；6-Amino-3-methyl-5-(phenylmethylamino)pyrimidine-2,4-dione；6-amino-5-(benzylamino)-3-methyl-1H-pyrimidine-2,4-dione
• CAS: 2034-31-3
• 化学式: C₁₂H₁₄N₄O₂
• 分子量: 246.269
• InChiKey: NZJRDZMLYKCMGH-UHFFFAOYSA-N

物化性质

• 熔点：
  211 °C
• 密度：
  1.34±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  87.5
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-amino-5-(benzylamino)-3-methylpyrimidine-2,4(1H,3H)-dione 在 palladium dihydroxide 4-二甲氨基吡啶 、 氯化亚砜 、 N-ethyl-N’-(diethylaminopropyl)-carbodiimide 、 ammonium formate 、 potassium carbonate 、 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 30.0h， 生成 (6aR,9aS)-5,6a,7,8,9,9a-hexahydro-5-methyl-2-(phenylmethyl)-3-[(2,3-dimethoxyphenyl)methyl]cyclopent[4,5]imidazo[2,1-b]purin-4(3H)-one
  参考文献：
  名称：

  Potent Tetracyclic Guanine Inhibitors of PDE1 and PDE5 Cyclic Guanosine Monophosphate Phosphodiesterases with Oral Antihypertensive Activity

  摘要：

  Tetracyclic guanines have been shown to be potent and selective inhibitors of the cGMP-hydrolyzing enzymes PDE1 and PDE5. In general, these compounds are inactive or only weakly active as inhibitors of PDE3, which is a major isozyme involved in cAMP hydrolysis. Structure-activity relationships are developed at N-1, C-2, N-3, and N-5 on the core nucleus. Compound 31, with an IC50 of 70 pM, is the most potent inhibitor of PDE1, while 50, with an IC50 of 4 nM, is the most potent inhibitor of PDE5. Compounds 20, 22, 30, and 50 are potent dual inhibitors with IC50 values below 30 nM for both PDE1 and PDE5. Compounds 12, 20, and 28 reduced blood pressure by more than 45 mmHg when administered orally at 10 mg/kg to the spontaneously hypertensive rat (SHR).

  DOI：

  10.1021/jm9608467
• 作为产物：
  描述：

  5,6-diamino-3-methylpyrimidine-2,4(1H,3H)-dione hydrochloride 在 镍 sodium hydroxide 、 氢气 作用下， 以 水 为溶剂， 反应 1.0h， 生成 6-amino-5-(benzylamino)-3-methylpyrimidine-2,4(1H,3H)-dione
  参考文献：
  名称：

  Fenn, David M.; Lister, John H., Australian Journal of Chemistry, 1980, vol. 33, # 8, p. 1611 - 1617

  摘要：

  DOI：

文献信息

• [EN] IMIDAZO [2,1-B] PURINE DERIVATIVES AS TRPA1 MODULATORS<br/>[FR] DÉRIVÉS D'IMIDAZO[2,1-B]PURINE EN TANT QUE MODULATEURS DE TRPA1
  申请人：GLENMARK PHARMACEUTICALS SA

  公开号：WO2009144548A1

  公开（公告）日：2009-12-03

  The present invention provides TRPA (Transient Receptor Potential subfamily A) modulators. In particular, compounds described herein are useful for treating or preventing diseases, conditions and/or disorders modulated by TRPAl (Transient Receptor Potential subfamily A, member 1) modulators. Also provided herein are processes for preparing compounds described herein, intermediates used in their synthesis, pharmaceutical compositions thereof, and methods for treating or preventing diseases, conditions and/or disorders modulated by TRPAl.

  本发明提供了TRPA（瞬时受体电位亚家族A）调节剂。具体而言，本文描述的化合物可用于治疗或预防由TRPAl（瞬时受体电位亚家族A，成员1）调节剂调节的疾病、症状和/或疾病。此外，本文还提供了制备本文描述的化合物的方法、用于合成的中间体、药物组合物以及用于治疗或预防由TRPAl调节的疾病、症状和/或疾病的方法。
• Synthesis and evaluation of potent and selective c-GMP phosphodiesterase inhibitors
  作者：Ginny Dai Ho、Silverman Lisa、Ana Bercovici、Chester Puchalski、Deen Tulshian、Yan Xia、Michael Czarniecki、Michael Green、Renee Cleven、Hongtao Zhang、Ahmad Fawzi

  DOI：10.1016/s0960-894x(98)00681-7

  日期：1999.1

  Syntheses and structure-activity relationships (SAR) of cGMP selective phosphodiesterase inhibitors are discussed. Potent and selective inhibitors are produced when the C-2 position of tetracyclic guanine 1 is substituted with alkyl chains containing six carbon atoms.

  讨论了cGMP选择性磷酸二酯酶抑制剂的合成及其构效关系（SAR）。当四环鸟嘌呤1的C-2​​位被含有六个碳原子的烷基链取代时，会产生有效的抑制剂。
• Polycyclic guanine derivatives
  申请人：Schering Corporation

  公开号：US05393755A1

  公开（公告）日：1995-02-28

  Novel polycylic guanine derivatives of the formula: ##STR1## wherein J is oxygen or sulfur, R.sup.1 is hydrogen, alkyl or alkyl substituted with aryl or hydroxy; R.sup.2 is hydrogen, aryl, heteroaryl, cycloalkyl, alkyl or alkyl substituted with aryl, heteroaryl, hydroxy, alkoxy, amino, monoalkyl amino or dialkylamino, or --(CH.sub.2).sub.m TCOR.sup.20 wherein m is an integer from 1 to 6, T is oxygen or --NH-- and R.sup.20 is hydrogen, aryl, heteroaryl, alkyl or alkyl substituted with aryl or heteroaryl; R.sup.3 is hydrogen, halo, trifluoromethyl, alkoxy, alkylthio, alkyl, cycloalkyl, aryl, aminosulfonyl, amino, monoalkylamino, dialkylamino, hydroxyalkylamino, aminoalkylamino, carboxy, alkoxycarbonyl or aminocarbonyl or alkyl substituted with awl, hydroxy, alkoxy, amino, monoalkylamino or dialkylamino; R.sup.a, R.sup.b, R.sup.c, and R.sup.d are defined in the specification; and n is zero or one. The compounds of formulas (I) and (I') are useful as antihypertensive, muscle relaxant and bronchodilating agents.

  式子：##STR1## 其中J为氧或硫，R1为氢，烷基或烷基上取代芳基或羟基；R2为氢，芳基，杂环芳基，环烷基，烷基或烷基上取代芳基，杂环芳基，羟基，烷氧基，氨基，单烷基氨基或双烷基氨基，或--(CH2)mTCOR20，其中m为1到6的整数，T为氧或--NH--，R20为氢，芳基，杂环芳基，烷基或烷基上取代芳基或杂环芳基；R3为氢，卤素，三氟甲基，烷氧基，烷硫基，烷基，环烷基，芳基，氨基磺酰基，氨基，单烷基氨基，双烷基氨基，羟基烷基氨基，氨基烷基氨基，羧基，烷氧羰基或氨基羰基或烷基上取代芳基，羟基，烷氧基，氨基，单烷基氨基或双烷基氨基；R.sup.a，R.sup.b，R.sup.c和R.sup.d在规范中定义；n为零或一。式（I）和（I'）的化合物可用作降压，肌肉松弛和支气管扩张剂。
• The Gif system as a tool in medicinal chemistry: The oxidation of Sch 57726 under GoAggIII conditions
  作者：Darío Doller、Samuel Chackalamannil、Andrew Stamford、Brian McKittrick、Michael Czarniecki

  DOI：10.1016/s0960-894x(97)00238-2

  日期：1997.6

  The usefulness of the GoAgg(III) reaction protocol in the determination of potential products of CP-450 enzyme metabolism is explored on Sch 57726, a selective c-GMP phosphodiesterase inhibitor. A single major ketone is found as product. In contrast, the reaction with m-CPBA affords a product of oxidative ring cleavage. (C) 1997 Elsevier Science Ltd.
• LISTER J. H., AUSTRAL. J. CHEM., 1979, 32, NO 2, 387-397
  作者：LISTER J. H.

  DOI：——

  日期：——